ComaETICNCT02798588
Improving Awakening Prognostication After Non Anoxic Coma Using PET-MRI in Intensive Care Unit
A study testing PET-MRI in people with Coma, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
In last decades, several advances in the neuro-intensive management have lead to decrease mortality in Intensive Care Units. A significant morbidity remains as patients survive after a traumatic coma with uncertain quality of awakening and a high risk of functional disability. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Coma
- What is being tested?
- PET-MRI
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteFrance
- Study dates
- 16 Feb 2017to 4 Jun 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting either vascular or traumatic lesions
- Patients with no response to simple command 48h after sedation's cessation
- Patients included between 7 days (to reduce the effect of early oedema) and 30 days after the coma (to control the homogeneity of our cohort)
- Patients included between 18 and 75 years old, to limit the risk of care withdrawal for poor previous medical condition
- Patients evaluated by a global electrophysiological assessment at beside in ICU in a short delay before or after PET-MRI
Who cannot join
- Patient with an associated anoxic encephalopathy
- Patients with contra-indication to MRI
- Patients with hypersensibility to the active molecules (FDG) or to one of this excipient
- Pregnant women
- Minor patients
- Patients under legal protection
Show all 10Show fewer
- Patients not affiliated to French health care system
- Patients in poor medical condition (hemodynamic, respiratory instability)
- Patients moribund or with previous decision of care withdrawal
- Absence of relatives to give written consent
Trial locations and contacts
1 site in 1 country.
France1 site
Réanimation polyvalente neurologique Hôpital Neurologique HCL
Bron, 69500
About this study
In last decades, several advances in the neuro-intensive management have lead to decrease mortality in Intensive Care Units. A significant morbidity remains as patients survive after a traumatic coma with uncertain quality of awakening and a high risk of functional disability. Predicting awareness recovery and functional disability of those who will awake constitutes a major challenge to inform patients' relatives, to give the best chances in terms of rehabilitation resources or to adapt intensive cares to a reasonable level. Tools currently available are not sufficient neither to predict bad awakening outcome nor to predict good functional outcome. In many countries, life's support cessation is a constant call for robust evaluation as soon as possible in ICU but it is mandatory to reach a positive predictive value of non-awaking close to 100%. Many clinical, electro-physiological, biological, radiological and functional parameters have been conducted with comatose patients assuming the purpose to predict outcome. Regarding unfavourable outcome, the gold standard is the abolition of the N20 component of somatosensory evoked potentials but the specificity is high enough only for patients with anoxic coma. Several neurophysiological markers such as MMN, P300 are correlated to a favourable outcome but the sensitivity and specificity remains low for patients who suffered a severe traumatic brain injury. New Diffusion Tensor imaging sequences provide complementary information to detect small structural lesions (diffuse axonal lesions). Recently, functional MRI analyzing Resting State has also been proposed as a prognostic marker during coma. PET using Fluoro-Desoxy-Glucose is able to assess the metabolism in key regions of the awakening network in either anaesthesia or sleep. Recent studies have reported interesting results at the chronic stage but to knowledge, these tools have only been used to address pathophysiology's issues and never to improve coma prognosis at the initial stage. The investigators hypothesize that the heterogeneity of the population requires a global and accurate assessment of the central nervous system, combining structural, metabolic and functional information in order to refine the prognosis.
The protocol integrates in one-sequence most radiological markers of brain injury within a unique PET-MRI in Lyon. The most relevant originality of the study consists in confronting FDG-PET and MRI sequences to a large clinical, electrophysiological and biological battery. The added clinical value would be to question the synergistic effect of each parameter and to find out which ones are the most useful for awakening prediction, as they have not been compared in a multi-parametric database.
Read more
PET-MRI, as a new device combining physiological and prognostic questioning, allows us:
- to implement a more integrative physio-pathological analysis
- to avoid the cofounding effect of awareness' fluctuations in recording simultaneously multiple functional imaging techniques.
The RS will be analyzed at 2 epochs in order to assess the stability of brain connectivity, related to neuronal activity (glucose metabolism) and brain perfusion.
- Conditions
- Coma
- Being tested
- PET-MRI
- Keywords
- coma, prognosis, comparative study, functional imaging, PET-MRI, electrophysiology
- Medical subject headings
- Coma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET-MRIRadiation
18Fluoro-Desoxy-Glucose's infusion for PET (glucose neural metabolism assessment, with quantitative information permitted by radioactivity monitoring through arterial catheter ; dosage = 1,5 MBq/Kg + 18,5 MBq as loading dose 5 min= Outside the scanner, Installation and movement management: Curare+/- sedative injection with standardized routine care protocol 10 min= Outside the scanner, Starting PET continuous acquisitionT= 0, Morphological MRI sequences- 3DT1, 3DFlair, T2SE, T2 HR on brainstem, Susceptibility and simple Diffusion Weighted Imaging-Specifically dedicated MR sequences based upon clinical issues 25 min, MRI in Resting state N°1 (global short-term functional connectivity)13 min, MRI DTI acquisition, 64 directions, sensitive to white matter injury 8 min, IRM in 2D-Arterial Spin Labelling:Quantitative Cerebral blood flow information (no Gadolinium)->8 min, IRM in Resting state 2 (repeated occurrence to assess stationarity) 13 min, End of PET continuous acquisition
| Study group | Role | What they receive |
|---|---|---|
| Comatose patients in ICU | Experimental | Not described Receives: Radiation: PET-MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of feasibility (pilot study) with Number of patients included during a 12-months period
Measured: at 12 months
Analysis of feasibility (pilot study) with ratio of patient included vs patient admissible according to the screening
Measured: at 12 months
Analysis of feasibility (pilot study) with respect of deadline for completion of PET MRI
Measured: at 12 months
Analysis of security (pilot study) with tolerance of the PET-MRI
Measured: at 12 months
Secondary outcomes (3)
Unfavorable clinical evolution towards awareness (dichotomic criteria : absence of awareness with functional communication)
Building a prognostic tool including miscellaneous parameters (clinical, biological, electrophysiological, metabolic PET and multimodal MRI) for the prediction of an unfavourable outcome (death, vegetative state, minimally conscious state) at 1 year after a non-anoxic brain injury (focal or multifocal; either traumatic or vascular causes)
Measured: at 12 month
Unfavorable clinical evolution in absence of awareness (ordinal criteria within unfavorable outcome) with Coma Recovery Scale-Revised
Defining an association of criteria, which are available in the 1st month after coma, that are able to predict at 1 year with a high positive predictive value the level of disorder of consciousness in the subgroup with unfavourable outcome in analyzing (according to Coma Recovery Scale-Revised) the evolution of :
- vegetative state patients
- minimally-conscious patients
- dead patients
Measured: at 12 month
Functional clinical evolution in presence of awareness (ordinal criteria within favorable outcome) according to Glasgow Outcome Scale (GOS)
Defining an association of criteria which are available in the 1st month after coma, that are able to predict at 1 year with a high positive predictive value the quality of functional outcome in the subgroup with favourable outcome in analyzing the level of autonomy according to Glasgow Outcome Scale (GOS)
Measured: at 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study start16 Feb 2017
- Primary completion4 Jun 2020
- Study completion4 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ComaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Florent GOBERT, MD, Principal investigator, Réanimation polyvalente neurologique Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02798588
- Sponsor's protocol ID
- 69HCL15_0669
- Other IDs
- 2015-A01886-43
- Acronym
- ETIC
- Status last verified
- Mar 2022
- First submitted
- 27 May 2016
- Last updated
- 7 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Awakening Prognostication After Non Anoxic Coma Using PET-MRI in Intensive Care Unit
- ClinicalTrials.gov ID
- NCT02798588
- Acronym / sponsor ID
- ETIC / 69HCL15_0669
- Conditions
- Coma
- Keywords
- coma, prognosis, comparative study, functional imaging, PET-MRI, electrophysiology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 16 Feb 2017 (actual)
- Primary completion
- 4 Jun 2020 (actual)
- Study completion
- 4 Jun 2020 (actual)
- First posted
- 14 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In last decades, several advances in the neuro-intensive management have lead to decrease mortality in Intensive Care Units. A significant morbidity remains as patients survive after a traumatic coma with uncertain quality of awakening and a high risk of functional disability. Predicting awareness recovery and functional disability of those who will awake constitutes a major challenge to inform patients' relatives, to give the best chances in terms of rehabilitation resources or to adapt intensive cares to a reasonable level. Tools currently available are not sufficient neither to predict bad awakening outcome nor to predict good functional outcome. In many countries, life's support cessation is a constant call for robust evaluation as soon as possible in ICU but it is mandatory to reach a positive predictive value of non-awaking close to 100%. Many clinical, electro-physiological, biological, radiological and functional parameters have been conducted with comatose patients assuming the purpose to predict outcome. Regarding unfavourable outcome, the gold standard is the abolition of the N20 component of somatosensory evoked potentials but the specificity is high enough only for patients with anoxic coma. Several neurophysiological markers such as MMN, P300 are correlated to a favourable outcome but the sensitivity and specificity remains low for patients who suffered a severe traumatic brain injury. New Diffusion Tensor imaging sequences provide complementary information to detect small structural lesions (diffuse axonal lesions). Recently, functional MRI analyzing Resting State has also been proposed as a prognostic marker during coma. PET using Fluoro-Desoxy-Glucose is able to assess the metabolism in key regions of the awakening network in either anaesthesia or sleep. Recent studies have reported interesting results at the chronic stage but to knowledge, these tools have only been used to address pathophysiology's issues and never to improve coma prognosis at the initial stage. The investigators hypothesize that the heterogeneity of the population requires a global and accurate assessment of the central nervous system, combining structural, metabolic and functional information in order to refine the prognosis.
The protocol integrates in one-sequence most radiological markers of brain injury within a unique PET-MRI in Lyon. The most relevant originality of the study consists in confronting FDG-PET and MRI sequences to a large clinical, electrophysiological and biological battery. The added clinical value would be to question the synergistic effect of each parameter and to find out which ones are the most useful for awakening prediction, as they have not been compared in a multi-parametric database.
PET-MRI, as a new device combining physiological and prognostic questioning, allows us:
- to implement a more integrative physio-pathological analysis
- to avoid the cofounding effect of awareness' fluctuations in recording simultaneously multiple functional imaging techniques.
The RS will be analyzed at 2 epochs in order to assess the stability of brain connectivity, related to neuronal activity (glucose metabolism) and brain perfusion.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Comatose patients in ICU | Experimental | Radiation: PET-MRI |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients presenting either vascular or traumatic lesions
- Patients with no response to simple command 48h after sedation's cessation
- Patients included between 7 days (to reduce the effect of early oedema) and 30 days after the coma (to control the homogeneity of our cohort)
- Patients included between 18 and 75 years old, to limit the risk of care withdrawal for poor previous medical condition
- Patients evaluated by a global electrophysiological assessment at beside in ICU in a short delay before or after PET-MRI
Key exclusion criteria (10 listed)
- Patient with an associated anoxic encephalopathy
- Patients with contra-indication to MRI
- Patients with hypersensibility to the active molecules (FDG) or to one of this excipient
- Pregnant women
- Minor patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PET-MRI18Fluoro-Desoxy-Glucose's infusion for PET (glucose neural metabolism assessment, with quantitative information permitted by radioactivity monitoring through arterial catheter ; dosage = 1,5 MBq/Kg + 18,5 MBq as loading dose 5 min= Outside the scanner, Installation and movement management: Curare+/- sedative injection with standardized routine care protocol 10 min= Outside the scanner, Starting PET continuous acquisitionT= 0, Morphological MRI sequences- 3DT1, 3DFlair, T2SE, T2 HR on brainstem, Susceptibility and simple Diffusion Weighted Imaging-Specifically dedicated MR sequences based upon clinical issues 25 min, MRI in Resting state N°1 (global short-term functional connectivity)13 min, MRI DTI acquisition, 64 directions, sensitive to white matter injury 8 min, IRM in 2D-Arterial Spin Labelling:Quantitative Cerebral blood flow information (no Gadolinium)->8 min, IRM in Resting state 2 (repeated occurrence to assess stationarity) 13 min, End of PET continuous acquisition | Radiation | Comatose patients in ICU |
Primary outcome
Analysis of feasibility (pilot study) with Number of patients included during a 12-months period
Time frame: at 12 months
Analysis of feasibility (pilot study) with ratio of patient included vs patient admissible according to the screening
Time frame: at 12 months
Analysis of feasibility (pilot study) with respect of deadline for completion of PET MRI
Time frame: at 12 months
Analysis of security (pilot study) with tolerance of the PET-MRI
Time frame: at 12 months
3 secondary outcomes
Unfavorable clinical evolution towards awareness (dichotomic criteria : absence of awareness with functional communication)
Time frame: at 12 month
Unfavorable clinical evolution in absence of awareness (ordinal criteria within unfavorable outcome) with Coma Recovery Scale-Revised
Time frame: at 12 month
Functional clinical evolution in presence of awareness (ordinal criteria within favorable outcome) according to Glasgow Outcome Scale (GOS)
Time frame: at 12 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Florent GOBERT, MD principal investigator
Réanimation polyvalente neurologique Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET-MRI in people with Coma, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analysis of feasibility (pilot study) with Number of patients included during a 12-months period (time frame: at 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2022.